For the millions of cancer survivors in the United States, emerging
from surgery cancer-free is the ultimate victory. But many patients
who clear the hurdle of cancer trauma will subsequently face a
lifetime of swelling and discomfort, caused by an untreatable
buildup of fluid in their tissues.

A team at the Stanford University School of Medicine has created an
animal model for this complex condition, called lymphedema, taking
the first steps toward understanding its behavior. Their results,
which will appear in the July 17 issue of Public Library of Science-
Medicine, indicate lymphedema is characterized not just by the
presence of swelling, but by a profound, accompanying inflammation.
This finding suggests drug therapies could one day be used to treat
this disease.

"Ten million people in the United States have lymphedema. It's
heartbreaking that the disease goes unacknowledged or unrecognized
because doctors simply have no treatment to offer," said Stanley
Rockson, MD, associate professor of medicine (cardiovascular) and
senior author of the study. "This study opens the door to the
likelihood of effective therapies."

Rockson said between 15 and 30 percent of breast cancer survivors
develop lymphedema from surgery-induced damage to the lymphatic
system -- a network of tissues and cells that make and store cells
to fight infection. When surgery disrupts this circulatory system,
protein-rich fluid collects in the tissue of the affected limb. This
stagnant liquid bloats the tissue and impairs limb mobility,
ultimately creating a cesspool for infection.

Current treatments for lymphedema involve bandaging the affected
area or wearing tight-fitting garments to compress the swelling.
Massaging can also help improve lymphatic flow. However, such
measures are temporary, Rockson said, and provide little relief.

"It's like the iron lung for polio -- it works, but it's certainly
no way to live," he said.

In this study, Rockson and his co-authors generated a mouse model to
simulate human-acquired lymphedema. The model was tested using
microscopic imaging and molecular-level techniques to find a
molecular fingerprint or signature of the disease. Mouse tails were
used for the model because of their rich lymphatic network -- a
simple substitute for the arm, according to Rockson.

The researchers were able to trace lymphatic cell flow by injecting
luciferase, the enzyme that gives fireflies their glow, into the
mouse tails. Using a dynamic imaging technique, the scientists
observed cell traffic slowing to a crawl in mice with lymphedema. At
the molecular level, the researchers used a microarray chip to
determine which of the mouse genes were active.

"Much to our delight, only 600 to 700 of the genes had changed,"
Rockson said, corresponding to about 1 percent of the 55,000 genes
in a mouse. "This will allow us to determine whether we can treat
lymphedema with a drug or compound that will revert the patient to
normal behavior."

"From a patient perspective, it's exciting to see that we are moving
beyond bandages and massage therapy," said Wendy Chaite, president
and founder of the Lymphatic Research Foundation, a nonprofit
organization based in East Hills, N.Y. Chaite, whose daughter was
born with lymphedema, founded the organization out of frustration
with the lack of treatment available for the disease.

"This study is a springboard for a lot of future investigations,"
she added. "Prior to this decade, people were not looking at this
disease from the standpoint of 21st-century tools and technologies."

Rockson said the next step is developing viable therapies for
humans. His team has targeted six classes of drugs for study, one of
which has already been tested.

"Within the next 12 to 24 months we could be at the stage of testing
in human populations," Rockson said.

Other Stanford authors include undergraduates Andrew An, Smita Joshi
and Ned Rockson; postdoctoral scholar Andreas Beilhack, MD; research
associate Jennifer Han, MD; cardiology fellow Raymond Tabibiazar,
MD; Roger Wagner, MD, PhD, instructor of cardiovascular medicine,
and Soheil Dadras, MD, assistant professor of medicine (pathology).
Medical students Lauren Cheung of the University of California-
Irvine and Jeffrey Swanson of the University of Pennsylvania were
also authors. The study was funded by the Susan G. Komen Breast
Cancer Foundation and the Western States Affiliate of the American
Heart Association.

Stanford University Medical Center integrates research, medical
education and patient care at its three institutions -- Stanford
University School of Medicine, Stanford Hospital & Clinics and
Lucile Packard Children's Hospital at Stanford. For more
information, please visit the Web site of the medical center's
Office of Communication & Public Affairs at Stanford University